JAK1/2 Inhibitor Baricitinib Improves Skin Fibrosis and Digital Ulcers in Systemic Sclerosis
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Zhanying Hou1,2, Xuehan Su1,3, Guangming Han4
1Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, China.
Background:
Systemic sclerosis (SSc) is a rare disabling connective tissue disease with few available treatment options. Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality. A previous experiment has shown that JAK2 inhibitor can significantly improve skin fibrosis in bleomycin (BLM)-induced murine model, including reducing dermal thickening and collagen accumulation. We aimed to describe the efficacy of oral JAK1/2 inhibitor baricitinib in SSc patients, especially focusing on skin fibrosis and microvascular manifestations.
Methods:
We described the different effects of oral selective JAK1, JAK2, or JAK3 inhibitor treatment in a BLM-induced skin fibrosis mouse model. Furthermore, 10 adult patients with dcSSc were treated with baricitinib. We assessed the changes in modified rodman skin score (mRSS) and digital ulcer net burden at week 12 and 24 from baseline. We also compared the absolute changes in scores on the Scleroderma Health Assessment Questionnaire (SHAQ) and a total score on the St. George's Respiratory Questionnaire (SGRQ) over a 24-week period.
Results:
In the experimental mouse model of skin fibrosis, a JAK1 and JAK2 inhibitor ameliorated skin fibrosis, and a JAK2 inhibitor had the most obvious effect. Treatment with the JAK2 inhibitor also blunted the capillary rarefaction. We demonstrated that skin fibrosis and digital ulcers were significantly relieved in 10 SSc patients treated with baricitinib. The mRSS significantly improved at week 12 from baseline, with a mean change in mRSS of -8.3 [95% confidence interval (CI), -12.03 to -4.574; p = 0.0007] and improved greater at week 24 to -11.67 (95% CI, -16.84 to -6.496; p = 0.0008). Among the four patients with digital ulcers (DU), three were completely healed at week 24, the number of ulcers in another patient was significantly reduced, and there was no patient with new ulcers. Only one adverse event (AE) of herpes zoster was observed.
Conclusions:
Our results indicate that selective JAK1 and JAK2 inhibitor alleviates skin fibrosis, and oral JAK1/2 inhibitor baricitinib is a potentially effective treatment for dcSSc patients with skin fibrosis and DU. Baricitinib was well-tolerated by most patients in this study. Additional large clinical trials are needed to confirm our pilot findings.
Chinese Clinical Trial Registry Number:
ChiCTR2000030995.
Insights
Baricitinib, a JAK1/2 inhibitor, shows promise in treating systemic sclerosis (SSc) by significantly improving skin fibrosis and healing digital ulcers in patients. This study highlights baricitinib as a potentially effective treatment for diffuse cutaneous systemic sclerosis (dcSSc).
Area of Science:
- Rheumatology
- Immunology
- Dermatology
Background:
- Systemic sclerosis (SSc) is a rare, disabling autoimmune disease characterized by fibrosis and microvascular damage, with limited therapeutic options.
- Diffuse cutaneous systemic sclerosis (dcSSc) presents a high mortality rate, underscoring the need for effective treatments.
- Previous research indicated JAK2 inhibitors could reduce skin fibrosis in a bleomycin-induced murine model.
Purpose of the Study:
- To evaluate the efficacy of oral baricitinib, a JAK1/2 inhibitor, in treating skin fibrosis and microvascular manifestations in patients with dcSSc.
- To assess the impact of baricitinib on key clinical indicators of SSc progression and patient-reported outcomes.
Main Methods:
- A study involving a bleomycin-induced skin fibrosis mouse model to test selective JAK inhibitors (JAK1, JAK2, JAK3).
- Ten adult patients with dcSSc received oral baricitinib treatment.
- Clinical assessments included modified Rodnan skin score (mRSS), digital ulcer (DU) burden, Scleroderma Health Assessment Questionnaire (SHAQ), and St. George's Respiratory Questionnaire (SGRQ) over 24 weeks.
Main Results:
- Baricitinib treatment significantly improved mRSS in dcSSc patients at weeks 12 and 24.
- Three out of four patients with digital ulcers experienced complete healing by week 24; another showed significant reduction.
- No new digital ulcers developed, and only one patient reported herpes zoster as an adverse event.
Conclusions:
- Oral baricitinib demonstrates potential as an effective treatment for skin fibrosis and digital ulcers in dcSSc patients.
- Baricitinib was generally well-tolerated, with a favorable safety profile observed in this pilot study.
- Larger clinical trials are warranted to validate these promising findings and confirm baricitinib's therapeutic role in SSc management.
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